ABSTRACT Invasive cervical cancer (ICC) kills 270,000 women/year, and 445,000 new cases are diagnosed annually. ICC is preventable with human papillomavirus (HPV) vaccination, cervical screening, and treatment of cervical dysplasia. However, 84% of new ICC cases occur in low-and-middle income countries (LMICs) such as Malawi, due to poor access to all three prevention strategies. This challenge is compounded in Sub-Saharan Africa (SSA), the epicenter of the HIV epidemic, because HIV-infected women are at increased risk for developing cervical dysplasia and have a >20-fold increased risk for ICC than HIV-uninfected women. In SSA, women comprise 59% of adults infected with HIV, and ICC is the most common cancer among women. The World Health Organization (WHO) recommends screening with high-risk (hr)-HPV testing/visual inspection with acetic acid (VIA) and treatment with cryotherapy as the preferred approach to prevent ICC in LMICs. Malawi has attempted to implement VIA and cryotherapy since 2004, but both screening and treatment rates remain abysmal. Furthermore, the HPV vaccine is not yet available in Malawi, and even when it does roll out in 2019, the vast majority of Malawian women will remain unvaccinated or age ineligible since, similar to other resource-limited SSA countries, only adolescent girls will be eligible for it. Even if widespread vaccination of adolescent girls is achieved, the consequent decline in ICC incidence is not anticipated for decades, and millions of African women will be missed. Therefore, an improved and scalable ICC prevention approach is urgently needed. We plan to evaluate a novel ICC screen-and-treat algorithm among HIV-infected women in Malawi with the following strategy: self-collected vaginal swabs for hr-HPV testing, followed by same-day VIA and cervical thermocoagulation for those who are VIA positive and eligible for ablation. This strategy has not yet been robustly evaluated, utilizes new technologies developed specifically for low-resource settings (rapid Xpert HPV testing, thermocoagulation), and can be completed in a single day. These attributes are likely to address the coverage and attrition problems that have limited current approaches. Specifically, Aim 1 will assess same-day completion of this novel ICC screen-and-treat strategy among 625 HIV-infected women in Malawi, enrolled over 12 months from antiretroviral therapy clinics in the capital city of Lilongwe. Aim 2 will evaluate the performance of the proposed screen-and-treat strategy among HIV-infected women, by estimating the overtreatment rate for women who are hr-HPV positive/VIA positive and the undertreatment rate among HIV-infected women who are hr-HPV positive/VIA negative. Aim 3 will determine the 24-week efficacy of thermocoagulation among HIV- infected women with high-grade cervical dysplasia (CIN2/3). This study will provide essential data to inform national policy in Malawi and other countries where both HIV and ICC prevalence are high, and it will also facilitate applications for future cooperative clinical trials groups in cervical cancer and global oncology.